Immunomodulatory Effects of Modified Atkins Diet in Patients With Multiple Sclerosis

A study on the effects of a modified Atkins diet (MAD) on patients with multiple sclerosis (MS) reveals significant changes in immune cell metabolism and anti-inflammatory responses, suggesting the potential for dietary interventions in MS therapy.

Previous research has shown that diet can impact immune processes in MS, and ketogenic diets have demonstrated anti-inflammatory effects in animal models of MS. However, the effects of these diets on humans with MS are still unclear. MAD is a less restrictive form of the ketogenic diet with established clinical use in refractory epilepsy, making it a promising dietary intervention to study in MS.

Researchers analyzed cryopreserved peripheral blood mononuclear cells (PBMCs) and plasma from 39 patients with relapsing MS before and after 6 months of adhering to a MAD. The samples were analyzed as matched pairs, comparing baseline and 6-month samples from each subject. PBMCs were analyzed using single-cell RNA sequencing (scRNAseq), flow cytometry, and ex vivo stimulation assays, while plasma samples underwent metabolomics and multiplex analysis.

Over 6 months, there were significant changes in peripheral immune subsets related to both innate and adaptive immunity. These changes included a decrease in proinflammatory phenotypes in myeloid cells, a shift from memory to naïve CD8 cells, an increase in abundance and suppressive activity of regulatory T cells, and a decrease in B-cell activation. MAD also significantly decreased plasma levels of proinflammatory cytokines and chemokines, like IL-6 and CCL2. This low-carbohydrate, high-fat diet appeared to shift the balance between glycolysis and fatty acid oxidation, as shown by gene and protein expression patterns and plasma metabolomics.

“Our findings support the immunomodulatory potential of ketogenic diets in MS, demonstrating the capacity of MAD to reprogram immune cell metabolism and promote anti-inflammatory phenotypes,” said researchers. “These results provide a rationale for larger, randomized studies comparing dietary interventions and evaluating clinical outcomes, with an ultimate goal of establishing nutritional guidelines as an adjunctive approach to MS therapy.” 

Reference
Godfrey W, Moreau G B, Lehner-Gulotta D, et al. A six-month ketogenic diet alters the immune and metabolic landscape in multiple sclerosis. Presented at: 2025 ACTRIMS Forum; February 27-March 1; West Palm, Beach, FL; Session LB1.2.